PUBLICATION
Evolution of the pregnane X receptor: adaptation to cross-species differences in biliary bile salts
- Authors
- Krasowski, M.D., Yasuda, K., Hagey, L.R., and Schuetz, E.G.
- ID
- ZDB-PUB-050221-10
- Date
- 2005
- Source
- Molecular endocrinology (Baltimore, Md.) 19(7): 1720-1739 (Journal)
- Registered Authors
- Keywords
- Nuclear hormone receptor, xenobiotics, cholestasis, positive selection, metabolism, molecular evolution
- MeSH Terms
-
- Receptors, Steroid/agonists*
- Receptors, Steroid/classification*
- Receptors, Steroid/genetics
- Humans
- Cholestanols/pharmacology
- Bile Acids and Salts/chemistry
- Bile Acids and Salts/pharmacology*
- Bile Acids and Salts/physiology
- Molecular Structure
- Xenopus laevis
- Receptors, Cytoplasmic and Nuclear/agonists*
- Receptors, Cytoplasmic and Nuclear/classification*
- Receptors, Cytoplasmic and Nuclear/drug effects
- Receptors, Cytoplasmic and Nuclear/genetics
- Evolution, Molecular*
- Xenopus Proteins/drug effects
- Zebrafish
- Species Specificity
- Animals
- Rabbits
- Rats
- Phylogeny
- Mice
- PubMed
- 15718292 Full text @ Mol. Endocrinol.
- CTD
- 15718292
Citation
Krasowski, M.D., Yasuda, K., Hagey, L.R., and Schuetz, E.G. (2005) Evolution of the pregnane X receptor: adaptation to cross-species differences in biliary bile salts. Molecular endocrinology (Baltimore, Md.). 19(7):1720-1739.
Abstract
The pregnane X receptor (PXR) regulates the metabolism and elimination of bile salts, steroids, and xenobiotics. The sequence of the PXR ligand-binding domain diverges extensively between different animals suggesting inter-species differences in ligands. Of the endogenous ligands known to activate PXR, biliary bile salts vary the most across vertebrate species, ranging from 27-carbon (C27) bile alcohol sulfates (early fish, amphibians) to C24 bile acids (birds, mammals). Using a luciferase-based reporter assay, human PXR was activated by a wide variety of bile salts. In contrast, zebrafish PXR was activated efficiently only by cyprinol sulfate, the major zebrafish bile salt, but not by recent bile acids. Chicken, mouse, rat, and rabbit PXRs were all activated by species-specific bile acids and by early fish bile alcohol sulfates. In addition, phylogenetic analysis using maximum likelihood demonstrated evidence for non-neutral evolution of the PXR ligand-binding domain. PXR activation by bile salts has expanded from narrow specificity for C27 bile alcohol sulfates (early fish) to a broader specificity for recent bile acids (birds, mammals). PXR specificity for bile salts has thus paralleled the increasing complexity of the bile salt synthetic pathway during vertebrate evolution, an unusual example of ligand-receptor co-evolution in the nuclear hormone receptor superfamily.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping